Growth and regression of hormone-dependent mammary tumors are the function of the intracellular interplay between cAMP and estrogen. The interplay between cAMP and estrogen was reflected in the change in the activities of cAMP-dependent versus cGMP-dependent protein kinases in response to cAMP- or estrogen-stimulation of tumor slices in vitro. The interplay between cAMP and estrogen is also involved in the functional differentiation of mammary gland and in the tumorigenicity of carcinogen-induced mammary tumors.